My research focus is to make vaccines using a plant expression system, and test and
improve vaccine efficacy in mouse models of disease. Plants are very easy to grow,
and the vector we use, based on Tobacco mosaic virus (TMV), is an effective driver of protein expression. In addition, we have been exploring
TMV as a carrier molecule for vaccine delivery. TMV is a rod shaped virus, and although
it is not infectious in mammalian cells, its size promotes uptake by mammalian immune
cells and after uptake it stimulates innate antiviral immune responses. We have exploited
these properties to promote improve immunity to weakly immunogenic subunit vaccine
antigens. Subunit proteins have the advantage of being easy to produce compared to
an inactivated whole virus or bacteria, but the disadvantage is that most subunit
proteins are very weakly immunogenic, and don't stimulate protective immunity on their
own. By associating subunit vaccine protein to the surface of TMV, we have been able
to promote antigen uptake and potent immunity to subunit vaccine proteins after vaccination
in mice. In one recent study, we were able to associate the influenza antigen Hemagglutinin
(HA) from H1N1 virus to the surface of TMV, and show single dose protection from a
mouse model of influenza virus challenge. Our goals are to show that this is a universal
characteristic of TMV-subunit vaccine fusions, by testing improved potency of subunit
vaccine proteins from HIV, plague, tularemia, and tuberculosis. We are also expanding
our initial observations of HA vaccine protection to other pandemic HA subtypes like
those from H5N1 or H7N9. I have active collaborations with a number of research scientists
outside of Touro to help test protective immunity in pathogen challenge studies.

In a second project, we are using TMV as a way to deliver nucleic acids
to immune cells, which has the advantage of streamlining antigen delivery so that
the host cells that take up the TMV particle are making the subunit vaccine protein.
This has the advantage of speed of production, and may foster improved immune response
by activating additional innate immune repsonse pathways in mammalian immune cells.
We have used TMV to deliver antigen encoding RNA, and have an ongoing program to assemble
the particles in plants.

Pending research support

“Plant-produced synthetic vaccines for the prevention of tuberculosis”

The major goals of the project will be to produce in vivo transencapsidation of Mycobacterium tuberculosis antigen RNAs in plants, to create
novel combinations of RNA and TMV-Mtb protein conjugates, and test vaccine potency
in mice, including pathogen challenge.

NIH/NIAID McCormick, Alison A., PI 04-2014 to 03-2019

1R01AI110438-01 $2,661,890 direct/$3,564,292 total

“Single dose subunit vaccines for pandemic Influenza”

The major goals of the project will be to develop a new type of influenza vaccine
using TMV-influenza subunit vaccine conjugations. Work will include HA antigen expression
and scale-up in plants, conjugation optimization, and vaccine potency testing in mice,
including pathogen challenge.

Touro University, McCormick, Alison A., Co-PI 02-2014
to 01-2015

Seed grant $50,000 direct/$100,000
total

The major goals of the project will be to develop a new type of tularemia vaccine
by creating 4 different TMV-subunit vaccine conjugations, and combining them as a
multivalent vaccine. Work will include conjugation optimization, vaccine potency testing
in mice, and stability testing. My colleague will further test vaccine potency by
pahtogen challenge.

Current research support

NIH/NIAID McCormick, Alison A., PI 02-2012 to 01-2014

1R03AI099584-01 $100,000 direct/$144,700 total

“Adaptation of a Novel RNA virus for vaccine use”

The major goals of the project will be to develop an RNA antigen delivery vector using
Flock House Virus RNA encapsidated by TMV coat protein, and test antigen expression
in vitro.

DTC McCormick, Alison A. (PI) 05-2013 to 1-2014

Company Sponsored Research $23,000 total

“Phase II: Antigen fusions to improve immunogenicity”

The major goal of the project is to assess conjugation reproducibility of TMV-influenza
HA antigen-virus fusions, and determine cross-clade reactivity of sera from immunized
mice.

Completed research support

Gates Grand Challenge McCormick, Alison A., PI 05-2012 to 10-2013

Synthetic Biology, OPP1059735 $100,000 direct/$110,000 total

“Plant-produced synthetic RNA vaccines”

The major goals of the project will be to develop an in vivo transencapsidation system in plants, to create novel combinations of RNA and TMV
coat protein for vaccine optimization in vivo.